Altered transport properties of pentamidine-resistant Leishmania donovani and L. amazonensis promastigotes
Pentamidine-resistant clones of Leishmania donovani and L. amazonensis promastigotes were developed by increase of the drug pressure in the culture medium and characterized. The resistant clones could grow in 40 and 20 microM pentamidine as determined for L. donovani and L. amazonensis, respectively...
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| Veröffentlicht in: | Parasitology research (1987) 1997, Vol.83 (5), p.413-418 |
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| container_title | Parasitology research (1987) |
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| creator | BASSELIN, M LAWRENCE, F ROBERT-GERO, M |
| description | Pentamidine-resistant clones of Leishmania donovani and L. amazonensis promastigotes were developed by increase of the drug pressure in the culture medium and characterized. The resistant clones could grow in 40 and 20 microM pentamidine as determined for L. donovani and L. amazonensis, respectively, with 50% inhibitory concentrations (IC50 values) being 140 and 60 microM, which were 18 and 75 times higher than those recorded for the parental clones, respectively. Biochemical analysis of the clones showed that the acquired pentamidine resistance was specific (no cross-resistance to unrelated drugs and no reversibility with verapamil) and stable in vitro and in vivo. Pentamidine resistance is related to decreased drug uptake and highly increased efflux in both clones of Leishmania spp., accompanied by an alteration in polyamine carriers. Furthermore, a modification of the uptake of pyrimidine nucleosides and several amino acids by these resistant clones indicates alterations in the surface membrane. |
| doi_str_mv | 10.1007/s004360050274 |
| format | Article |
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The resistant clones could grow in 40 and 20 microM pentamidine as determined for L. donovani and L. amazonensis, respectively, with 50% inhibitory concentrations (IC50 values) being 140 and 60 microM, which were 18 and 75 times higher than those recorded for the parental clones, respectively. Biochemical analysis of the clones showed that the acquired pentamidine resistance was specific (no cross-resistance to unrelated drugs and no reversibility with verapamil) and stable in vitro and in vivo. Pentamidine resistance is related to decreased drug uptake and highly increased efflux in both clones of Leishmania spp., accompanied by an alteration in polyamine carriers. Furthermore, a modification of the uptake of pyrimidine nucleosides and several amino acids by these resistant clones indicates alterations in the surface membrane.</description><identifier>ISSN: 0932-0113</identifier><identifier>EISSN: 1432-1955</identifier><identifier>DOI: 10.1007/s004360050274</identifier><identifier>PMID: 9197387</identifier><identifier>CODEN: PARREZ</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Amino Acids - metabolism ; Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiparasitic agents ; Antiprotozoal Agents - metabolism ; Antiprotozoal Agents - pharmacology ; Biological and medical sciences ; Biological Transport ; Drug Resistance ; Leishmania donovani - drug effects ; Leishmania donovani - growth & development ; Leishmania mexicana - drug effects ; Leishmania mexicana - growth & development ; Medical sciences ; Nucleosides - metabolism ; Pentamidine - metabolism ; Pentamidine - pharmacology ; Pharmacology. 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The resistant clones could grow in 40 and 20 microM pentamidine as determined for L. donovani and L. amazonensis, respectively, with 50% inhibitory concentrations (IC50 values) being 140 and 60 microM, which were 18 and 75 times higher than those recorded for the parental clones, respectively. Biochemical analysis of the clones showed that the acquired pentamidine resistance was specific (no cross-resistance to unrelated drugs and no reversibility with verapamil) and stable in vitro and in vivo. Pentamidine resistance is related to decreased drug uptake and highly increased efflux in both clones of Leishmania spp., accompanied by an alteration in polyamine carriers. Furthermore, a modification of the uptake of pyrimidine nucleosides and several amino acids by these resistant clones indicates alterations in the surface membrane.</description><subject>Amino Acids - metabolism</subject><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiparasitic agents</subject><subject>Antiprotozoal Agents - metabolism</subject><subject>Antiprotozoal Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Biological Transport</subject><subject>Drug Resistance</subject><subject>Leishmania donovani - drug effects</subject><subject>Leishmania donovani - growth & development</subject><subject>Leishmania mexicana - drug effects</subject><subject>Leishmania mexicana - growth & development</subject><subject>Medical sciences</subject><subject>Nucleosides - metabolism</subject><subject>Pentamidine - metabolism</subject><subject>Pentamidine - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Polyamines - metabolism</subject><issn>0932-0113</issn><issn>1432-1955</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEtLxDAUhYMoOj6WLoUsxF3Hm6aZtEsRXzDgRtclTW410iY1NyPor7fiILi6B87HufAxdipgKQD0JQFUcgWgoNTVDluISpaFaJTaZQto5gxCyAN2SPQGIPSqqvbZfiMaLWu9YG9XQ8aEjudkAk0xZT6lOGHKHonHnk8Yshm98wGLhOQpm5D5Gj29jiZ4w10M8WNO3ATH10tuRvMVA4YZ_ZkaDWX_EjPSMdvrzUB4sr1H7Pn25un6vlg_3j1cX60LK4XOhRLGVra3WivZaSlhpbpOWyuUlGVlFVpwnZSVRBDSWuwRrXW1cXXpStHV8ohd_O7O3983SLkdPVkcBhMwbqjVDTRQ12oGi1_QpkiUsG-n5EeTPlsB7Y_b9p_bmT_bDm-6Ed0fvZU59-fb3pA1Qz8btZ7-sFILEGolvwEs9IOn</recordid><startdate>1997</startdate><enddate>1997</enddate><creator>BASSELIN, M</creator><creator>LAWRENCE, F</creator><creator>ROBERT-GERO, M</creator><general>Springer</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>1997</creationdate><title>Altered transport properties of pentamidine-resistant Leishmania donovani and L. amazonensis promastigotes</title><author>BASSELIN, M ; LAWRENCE, F ; ROBERT-GERO, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c317t-51ac4cfc7753b733065bb7cc153324c5ec0db3343e013ccefeeccd8ad82d21b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Amino Acids - metabolism</topic><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiparasitic agents</topic><topic>Antiprotozoal Agents - metabolism</topic><topic>Antiprotozoal Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Biological Transport</topic><topic>Drug Resistance</topic><topic>Leishmania donovani - drug effects</topic><topic>Leishmania donovani - growth & development</topic><topic>Leishmania mexicana - drug effects</topic><topic>Leishmania mexicana - growth & development</topic><topic>Medical sciences</topic><topic>Nucleosides - metabolism</topic><topic>Pentamidine - metabolism</topic><topic>Pentamidine - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Polyamines - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BASSELIN, M</creatorcontrib><creatorcontrib>LAWRENCE, F</creatorcontrib><creatorcontrib>ROBERT-GERO, M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Parasitology research (1987)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BASSELIN, M</au><au>LAWRENCE, F</au><au>ROBERT-GERO, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered transport properties of pentamidine-resistant Leishmania donovani and L. amazonensis promastigotes</atitle><jtitle>Parasitology research (1987)</jtitle><addtitle>Parasitol Res</addtitle><date>1997</date><risdate>1997</risdate><volume>83</volume><issue>5</issue><spage>413</spage><epage>418</epage><pages>413-418</pages><issn>0932-0113</issn><eissn>1432-1955</eissn><coden>PARREZ</coden><abstract>Pentamidine-resistant clones of Leishmania donovani and L. amazonensis promastigotes were developed by increase of the drug pressure in the culture medium and characterized. The resistant clones could grow in 40 and 20 microM pentamidine as determined for L. donovani and L. amazonensis, respectively, with 50% inhibitory concentrations (IC50 values) being 140 and 60 microM, which were 18 and 75 times higher than those recorded for the parental clones, respectively. Biochemical analysis of the clones showed that the acquired pentamidine resistance was specific (no cross-resistance to unrelated drugs and no reversibility with verapamil) and stable in vitro and in vivo. Pentamidine resistance is related to decreased drug uptake and highly increased efflux in both clones of Leishmania spp., accompanied by an alteration in polyamine carriers. Furthermore, a modification of the uptake of pyrimidine nucleosides and several amino acids by these resistant clones indicates alterations in the surface membrane.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>9197387</pmid><doi>10.1007/s004360050274</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0932-0113 |
| ispartof | Parasitology research (1987), 1997, Vol.83 (5), p.413-418 |
| issn | 0932-0113 1432-1955 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_79090885 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Amino Acids - metabolism Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiparasitic agents Antiprotozoal Agents - metabolism Antiprotozoal Agents - pharmacology Biological and medical sciences Biological Transport Drug Resistance Leishmania donovani - drug effects Leishmania donovani - growth & development Leishmania mexicana - drug effects Leishmania mexicana - growth & development Medical sciences Nucleosides - metabolism Pentamidine - metabolism Pentamidine - pharmacology Pharmacology. Drug treatments Polyamines - metabolism |
| title | Altered transport properties of pentamidine-resistant Leishmania donovani and L. amazonensis promastigotes |
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